We have obtained experimental evidence to support the conclusion that soy phytoestrogens may be a useful alternative to traditional hormone replacement therapy for females. We also have evidence from a study in young cynomolgus males that the soy phytoestrogens may be cardioprotective and that they do not affect the reproductive system of pre- and peripubertal males. Our concentration on postmenopausal females and soy phytoestrogens has increased our awareness of the public health importance of the simultaneous potential protective effects of soy phytoestrogens on coronary heart disease and hormone dependent cancers. That has caused us to pursue the possibility that soy phytoestrogens given to males will be cardioprotective, have no adverse effects on the reproductive system, and may provide protection against prostate cancer. We propose to intensify our pharmacologic studies of the soy phytoestrogens. We will use both postmenopausal females and males in this study in order to assess treatment effects on the cardiovascular system and reproductive system of both genders and bone metabolism biomarkers in females. This study will utilize 6 groups of 5 surgically menopausal female monkeys and 6 groups of 5 mature male monkeys assigned to a series of short-term Latin Square designs. The studies will assess the effects of varying doses, forms, and ratios of the phytoestrogens on intermediate outcomes. The specific questions to be addressed in this project are as follow: What is the peptide fraction in soy protein that is required for the isoflavones to have their effect on lipid metabolism? We will test whether the high molecular weight fraction or the 7S peptides of soy protein are required for the isoflavones to be effective. Are there differences on outcomes with soy phytoestrogen preparations that are predominately genistein or predominately daidzein? What is the relationship between dose of soy phytoestrogens (SPE) and outcomes?